Many of the germacranolide sesquiterpenes possess significant in vitro or in vivo anticancer activity, including the compounds eupaserrin, eriofertopin and elphantopin. These potentially useful substances cannot be obtained from natural sources in appreciable quantities, and so it is the object of this research to develop efficient syntheses of these and related germacranolides. A unified approach is sought, one based upon a novel synthetic route to costunolide, the simplest germacraolide of this class, which is currently under study in our laboratory. It involves synthesis of a suitably substituted 2,3-divinylcyclohexanol which is Cope rearranged to a cyclodecadiene structure; the normally unfavored large ring is trapped by an orthoester Claisen rearrangement of the cyclodecadiene, occurring under the Cope rearrangement conditions. An allylic sulfoxide to allylic alcohol rearrangement completes a key three step sequence, which provides both the cyclodecadiene ring and gamma-lactone common to all these germacranolides. The focus of this research will be, then, to develop modifications of this basic scheme which will allow synthesis of more highly functionalized germacrenes than costunolide. It is planned that at least eight anticancer germacranolides, never before synthesized, will be prepared during the course of this research.